Ventricular pacing to augment atrial natriuretic hormone production

ABSTRACT

Intermittent delivery of ventricular pacing pulses synchronized to occur during an atrial diastole time period can be used to provide atrial stretch therapy and augment the production and release of atrial natriuretic hormone.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application No.61/286,532, filed on Dec. 15, 2009, under 35 U.S.C. §119(e), which isincorporated herein by reference in its entirety.

BACKGROUND

Atrial natriuretic hormone (ANH)—also referred to as atrial natriureticpeptide (ANP), atrial natriuretic factor (ANF), or atriopeptin—is apolypeptide hormone involved in the homeostatic regulation of bodywater, sodium, and potassium. ANH is produced, stored, and secreted fromatrial myocytes in response to a variety of physiological signals,including atrial stretch, hypervolemia, and stimulation of thesympathetic nervous system, for example. ANH can cause vasodilation anddiuresis in response to increased blood pressure and volume.Furthermore, ANH can help inhibit hypertrophy and fibrosis of themyocardium—often referred to as “remodeling”—which can occur during orafter an ischemic event, for example. It is also believed that ANH caninhibit the renin-angiotensin-aldosterone system (RAAS), therebyreducing fluid overload and preventing or inhibiting maladaptive cardiacremodeling. Thus, ANH can benefit heart failure patients by reducing thestress of blood volume overload on the heart, as well as inhibitingcardiac remodeling.

OVERVIEW

This document describes, among other things, intermittent delivery ofventricular pacing pulses synchronized to occur during an atrialdiastole time period to provide atrial stretch therapy and augment theproduction and release of atrial natriuretic hormone.

Example 1 can include an apparatus comprising a cardiac rhythmmanagement device comprising: a ventricular pacing circuit, configuredto deliver a ventricular pace; and a processor circuit, coupled to theventricular pacing circuit, the processor configured to comprise a firstoperating mode, the processor configured to time delivery of theventricular pace, when in the first operating mode, such that: (1)delivery of the ventricular pace is synchronized to occur during anatrial diastole time period, and (2) delivery of the ventricular paceresults in a substantial overlap of ventricular systole and atrialsystole.

In Example 2, the subject matter of Example 1 can optionally include theprocessor being configured to time delivery of the ventricular pace,when in the first operating mode, to cause atrioventricular valveclosure during at least one of: early atrial systole or a specifiedperiod of time before atrial systole.

In Example 3, the subject matter of any one of Examples 1-2 canoptionally include an atrial pacing circuit configured to deliver anatrial pace, and wherein the atrial pacing circuit is coupled to theprocessor; and wherein the processor is configured to time delivery ofthe ventricular pace, when in the first operating mode, such that apaced ventricular contraction occurs before a paced atrial contractionduring the same cardiac cycle.

In Example 4, the subject matter of any one of Examples 1-3 canoptionally include an atrial sensing circuit, coupled to the processor,and configured to sense an atrial heart signal, and wherein the atrialsensing circuit is coupled to the processor; and wherein the processoris configured to time delivery of the ventricular pace, when in thefirst mode of operation, such that a paced ventricular contractionoccurs before a sensed atrial contraction during the same cardiac cycle.

In Example 5, the subject matter of any one of Examples 1-3 canoptionally include the processor being configured to time delivery ofthe ventricular pace, when in the first mode of operation, such that apaced ventricular contraction is substantially concurrent with a pacedor sensed atrial contraction during the same cardiac cycle.

In Example 6, the subject matter of any one of Examples 1-5 canoptionally include: a physiologic sensor, coupled to the processor, thephysiologic sensor configured to measure a physiologic parameter of asubject; wherein the processor is configured to adjust use of the firstoperating mode using information about the measure of the physiologicparameter.

In Example 7, the subject matter of any one of Examples 1-6 canoptionally include: a physical activity sensor, coupled to theprocessor, the physical activity sensor configured to detect physicalactivity of a subject; wherein the processor is configured to limit useof the first mode of operation to when the physical activity is above aspecified threshold value.

In Example 8, the subject matter of any one of Examples 1-7 canoptionally include a cardiac output monitor circuit, coupled to theprocessor, the cardiac output monitor circuit configured to provide anindication of a cardiac output of the subject; and wherein the processoris configured to limit use of the first mode of operation to when theindication of the cardiac output is below a specified threshold value.

In Example 9, the subject matter of any one of Examples 1-8 canoptionally include: a fluid status monitor circuit, coupled to theprocessor, the fluid status monitor circuit configured to monitor afluid status providing an indication of a fluid status of the subject;and wherein the processor is configured to use information about thefluid status of the subject to trigger use of the first operating mode.

In Example 10, the subject matter of any one of Examples 1-9 canoptionally include the processor being configured to adjust use of thefirst operating mode when the fluid status indicates at least one of:(1) a fluid overload condition, or (2) a fluid underload condition.

In Example 11, the subject matter of any one of Examples 1-10 canoptionally include a fluid status monitor circuit that is configured tomonitor the fluid status using a pulmonary artery pressure (PAP) signalreceived from a PAP sensor.

In Example 12, the subject matter of any one of Examples 1-11 canoptionally include the processor circuit being configured to alter adelivery time of the ventricular pace, when in the first operating mode,to provide variability, with respect to an atrial contraction time, overa plurality of the ventricular paces.

In Example 13, the subject matter of any one of Examples 1-12 canoptionally include the processor being configured to alter a ventricularpacing site, such as to inhibit or prevent accommodation of the subjectto the first operating mode.

In Example 14, the subject matter of any one of Examples 1-13 canoptionally include the processor being configured to adjust delivery ofa therapy to offset a decrease in cardiac output otherwise associatedwith the first operating mode.

In Example 15, the subject matter of any one of Examples 1-14 canoptionally include the processor being configured to at least one oftrigger or inhibit the first operating mode at least in part usinginformation about a detected physiological condition.

In Example 16, the subject matter of any one of Examples 1-15 canoptionally include the processor being configured to at least one oftrigger or inhibit the first operating mode at least in part usinginformation about a time of day.

In Example 17, the subject matter of any one of Examples 1-16 canoptionally include the processor being configured to at least one oftrigger or inhibit the first operating mode at least in part usinginformation about a posture.

In Example 18, the subject matter of any one of Examples 1-17 canoptionally include the processor being configured to at least one oftrigger or inhibit the first operating mode at least in part usinginformation about a sleep state.

Example 19 can include, or can optionally be combined with the subjectmatter of any one of Examples 1-18 to include an apparatus comprising acardiac rhythm management device comprising: a ventricular pacingcircuit, configured to deliver a ventricular pace; a processor circuit,coupled to the ventricular pacing circuit, the processor configured tocomprise a first operating mode, the processor configured to timedelivery of the ventricular pace, when in the first operating mode, suchthat: (1) delivery of the ventricular pace is synchronized to occurduring an atrial diastole time period, (2) delivery of the ventricularpace results in a substantial overlap of ventricular systole and atrialsystole, and (3) atrioventricular valve closure is caused during atleast one of: early atrial systole or a specified period of time beforeatrial systole; a physiologic sensor, coupled to the processor, thephysiologic sensor configured to measure a physiologic parameter of asubject including a physical activity, a cardiac output, and a fluidstatus; wherein the processor is configured to adjust use of the firstoperating mode using information about the measure of the physiologicparameter, including using information about the fluid status andincluding limiting use of the first mode of operation to when thephysical activity is above a specified threshold value and to whencardiac output is below a specified threshold value; and wherein theprocessor is configured to provide variability in the first operatingmode to inhibit or prevent accommodation of the subject to the firstoperating mode.

In Example 20, the subject matter of any one of Examples 1-19 canoptionally include the processor being configured to adjust delivery ofa therapy to offset a decrease in cardiac output otherwise associatedwith the first operating mode.

In Example 21, the subject matter of any one of Examples 1-20 canoptionally include the processor is configured to at least one oftrigger or inhibit the first operating mode at least in part using timeof day, posture, or sleep status information.

Example 22 can include, or can optionally be combined with the subjectmatter of any one of Examples 1-21 to include an apparatus comprising acardiac rhythm management device comprising: a ventricular pacingcircuit, configured to deliver a ventricular pace; a processor circuit,coupled to the ventricular pacing circuit, the processor configured tocomprise a first operating mode, the processor configured to timedelivery of the ventricular pace, when in the first operating mode, suchthat: (1) delivery of the ventricular pace is synchronized to occurduring an atrial diastole time period, and (2) delivery of theventricular pace results in a substantial overlap of ventricular systoleand atrial systole; an atrial pacing circuit configured to deliver anatrial pace, and wherein the atrial pacing circuit is coupled to theprocessor; and wherein the processor is configured to time delivery ofthe ventricular pace, when in the first operating mode, such that apaced ventricular contraction occurs before or substantially concurrentwith a paced atrial contraction during the same cardiac cycle.

Example 23 can include, or can optionally be combined with the subjectmatter of one of Examples 1-22 to include a method comprising: using acardiac rhythm management device, delivering a ventricular pace to aventricle of a subject when in a first operating mode; and timingdelivery of the ventricular pace, when in the first operating mode, suchthat: (1) delivery of the ventricular pace is synchronized to occurduring an atrial diastole time period, and (2) delivery of theventricular pace results in a substantial overlap of ventricular systoleand atrial systole.

In Example 24, the subject matter of any one of Examples 1-23 canoptionally include timing delivery of the ventricular pace, when in thefirst operating mode, includes timing delivery of the ventricular paceto cause atrioventricular valve closure during at least one of: earlyatrial systole or a specified period of time before atrial systole.

In Example 25, the subject matter of any one of Examples 1-24 canoptionally include timing delivery of the ventricular pace, when in thefirst operating mode, comprises delivering the ventricular pace suchthat a paced ventricular contraction occurs before a paced atrialcontraction during the same cardiac cycle.

In Example 26, the subject matter of any one of Examples 1-25 canoptionally include timing delivery of the ventricular pace, when in thefirst operating mode, comprises delivering the ventricular pace suchthat a paced ventricular contraction occurs before a sensed atrialcontraction during the same cardiac cycle.

In Example 27, the subject matter of any one of Examples 1-25 canoptionally include timing delivery of the ventricular pace, when in thefirst operating mode, comprising delivering the ventricular pace suchthat a paced ventricular contraction is substantially concurrent with apaced or sensed atrial contraction during the same cardiac cycle.

In Example 28, the subject matter of any one of Examples 1-27 canoptionally include: detecting a measure of a physiological parameter ofthe subject; and adjusting use of the first operating mode usinginformation about the measure of the physiological parameter.

In Example 29, the subject matter of any one of Examples 1-28 canoptionally include detecting a physical activity of the subject; andlimiting use of the first mode of operation to when the physicalactivity is above a specified threshold value.

In Example 30, the subject matter of any one of Examples 1-29 canoptionally include monitoring a fluid status providing an indication ofa fluid status of the subject; and using information about the fluidstatus of the subject to trigger use of the first operating mode.

In Example 31, the subject matter of any one of Examples 1-30 canoptionally include adjusting use of the first operating mode when thefluid status indicates at least one of: (1) a fluid overload condition,or (2) a fluid underload condition.

In Example 32, the subject matter of any one of Examples 1-31 canoptionally include monitoring the fluid status comprises monitoringinformation about a pulmonary artery pressure (PAP).

In Example 33, the subject matter of any one of Examples 1-32 canoptionally include altering a delivery time of the ventricular pace,when in the first operating mode, to provide variability, with respectto an atrial contraction time, over a plurality of the ventricularpaces.

In Example 34, the subject matter of any one of Examples 1-33 canoptionally include adjusting delivery of a therapy to offset a decreasein cardiac output otherwise associated with the first operating mode.

In Example 35, the subject matter of any one of Examples 1-34 canoptionally include at least one of triggering or inhibiting the firstoperating mode at least in part using information about a detectedphysiological condition.

In Example 36, the subject matter of any one of Examples 1-35 canoptionally include at least one of triggering or inhibiting the firstoperating mode at least in part using information about a time of day.

In Example 37, the subject matter of any one of Examples 1-36 canoptionally include at least one of triggering or inhibiting the firstoperating mode at least in part using information about a posture.

In Example 38, the subject matter of any one of Examples 1-37 canoptionally include at least one of triggering or inhibiting the firstoperating mode at least in part using information about a sleep state.

These examples can be combined in any permutation or combination. Thisoverview is intended to provide an overview of subject matter of thepresent patent application. It is not intended to provide an exclusiveor exhaustive explanation of the invention. The detailed description isincluded to provide further information about the present patentapplication.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, which are not necessarily drawn to scale, like numeralsmay describe similar components in different views. Like numerals havingdifferent letter suffixes may represent different instances of similarcomponents. The drawings illustrate generally, by way of example, butnot by way of limitation, various embodiments discussed in the presentdocument.

FIG. 1 is a schematic diagram illustrating generally an example of animplantable or other ambulatory cardiac rhythm management (CRM) device.

FIG. 2 is a block diagram illustrating generally an example of portionsof the CRM device electronics unit.

FIGS. 3A-3C are schematic diagrams illustrating generally examples ofspecialized ventricular pacing used to provide atrial stretch therapy.

FIG. 4 is a schematic diagram illustrating generally an example ofspecialized ventricular pacing used to provide atrial stretch therapy.

FIG. 5 is a flow chart illustrating generally a method for deliveringatrial stretch therapy via intermittent specialized ventricular pacing.

DETAILED DESCRIPTION

The present inventors have recognized, among other things, that thetiming of ventricular pacing pulse delivery can be adjusted, such as tointermittently stretch the atria, thereby inducing the production andrelease of ANH. For example, delivery of ventricular pacing pulses thatare synchronized to occur during atrial diastole can cause atrial andventricular systoles to substantially overlap. In other words, suchtiming of ventricular pacing can result in the in the atria contractingagainst closed atrioventricular (AV) valves. This can cause an increasein atrial pressure, stretching of the atrial myocardium, and,consequently, augmented production and secretion of ANH.

Such ventricular pacing, synchronized to occur during atrial diastoleand intended to augment the release of ANH, can result in at leastpartial overlap of atrial and ventricular systoles. Although existingdevices and algorithms can provide ventricular pacing during atrialdiastole, they typically do not cause an overlap of atrial andventricular systoles. Existing devices, however, could easily bemodified, for example, such as by programming the AV delay to be longerthan an atrial systole time period, thereby resulting in overlap ofatrial and ventricular systoles.

FIG. 1 shows an example of an implantable or other ambulatory cardiacrhythm management (CRM) device 100. In an example, the CRM device 100can include an electronics unit 102 that can include ahermetically-sealed biocompatible housing 104 and a header 106 extendingtherefrom. The housing 104 can carry a power source and electronics. Theheader 106 can include one or more receptacles, such as for receivingthe proximal ends of intravascular leads 108A-C. In an example, the lead108A can be an intravascular RV lead that can extend from the superiorvena cava (SVC) into the right atrium (RA), and then into the rightventricle (RV). The lead 108A can include an RV apical tip electrode110, a slightly more proximal RV ring electrode 112, a still slightlymore proximal RV shock coil electrode 114, and an even more proximal RAor SVC shock coil electrode 116. The various electrodes can be used fordelivering electrical energy or sensing intrinsic electrical heartsignals. An intravascular CS/LV lead 108C can extend from the SVC intothe RA, through a coronary sinus (CS) into the coronary vasculature,such as near a portion of a left ventricle (LV). In an example, thissecond CS/LV lead 108C can include at least a distal electrode 118 and aproximal electrode 120, from which electrostimulation energies can bedelivered or intrinsic electrical heart signals can be sensed. Anintravascular right atrial (RA) lead 108B can extend from the SVC intothe RA, and can include a distal electrode 119 and a proximal electrode121. Other electrodes (e.g., a housing electrode 105 on the housing 104,a header electrode 107 on the header 106, an epicardial electrode, asubcutaneous electrode located away from the heart, or an electrodelocated elsewhere) or leads can be used.

In an example, an implantable CRM device 100 can include a communicationcircuit, such as to wireless communicate unidirectionally orbidirectionally with an external local interface 121, such as a CRMdevice programmer, repeater, handheld device, or the like. The localinterface 121 can be configured to communicate via a wired or wirelesscomputer or communication network 122 to a remote interface 124, such asa remote computer or server or the like.

FIG. 2 shows an example of portions of the CRM device electronics unit102. In an example, this can include a switching circuit 200, such asfor selectively connecting to the various electrodes such as on theleads 108A-C or elsewhere. An atrial sensing circuit 202 and aventricular sensing circuit 206 can be selectively coupled to variouselectrodes by the switching circuit 200, and can include senseamplifiers, filter circuits, other circuits such as for sensingintrinsic electrical signals, such as intrinsic heart signals. An atrialpacing circuit 204 and a ventricular pacing circuit 208 can beselectively coupled to various electrodes by the switching circuit 200,and can include pacing energy generation circuitry (e.g., capacitive,inductive, or other) such as for generating, storing, or delivering anelectrostimulation or other energy. An impedance measurement circuit 210can be selectively coupled to various electrodes by the switchingcircuit 200, such as for measuring a lead impedance, a tissue impedance,a regional or organ impedance, or other impedance. Impedancemeasurements can be used, for example, to determine a fluid status or arespiration parameter. Another circuit for monitoring one or both ofthese parameters can additionally or alternatively be included in theCRM device 100. For example, for monitoring fluid status, a pulmonaryartery pressure (PAP) sensor interface circuit can be used to receivePAP information from a PAP sensor. Examples of using a PAP sensor aredescribed in Stahmann U.S. patent application Ser. No. 11/249,624,entitled “METHOD AND APPARATUS FOR PULMONARY ARTERY PRESSURE SIGNALISOLATION,” filed on Oct. 13, 2005, now issued as U.S. Pat. No.7,566,308, assigned to Cardiac Pacemakers, Inc., which is incorporatedherein by reference in its entirety, including its description ofobtaining PAP information. In an example, the atrial sensing circuit202, the atrial pacing circuit 204, the ventricular sensing circuit 206,the ventricular pacing circuit 208, or the impedance circuit 210 can becoupled to a processor circuit 212. In an example, the processor 212 canperform instructions, such as for signal processing of signals derivedby the atrial sensing circuit 202, the ventricular sensing circuit 206,or the impedance circuit 210, or for controlling operation of the atrialpacing circuit 204, the ventricular pacing circuit 208, or otheroperations of the CRM device 100. In an example, the processor 212 canbe coupled to or include a physical activity sensor, such as anaccelerometer 214, configured to sense a patient's physical activitylevel. In an example, the accelerometer 214 can further be configured tosense heart sounds or posture. In an example, the processor 212 can becoupled to or include a physiologic sensor interface, such as a chemicalsensor interface 216, configured to communicate with a chemical sensor.Examples of chemical sensors that can be used in conjunction with CRMdevice 100 include sensors configured to measure blood gases,electrolytes, creatinine, blood urea nitrogen, glucose, and natriureticpeptides, among other things. The processor 212 can also be coupled toor include a memory circuit 218, such as for storing or retrievinginstructions or data, or a communication circuit 220, such as forcommunicating with the local interface 121.

CRM device 100 can be configured to operate in a normal operating modeor an ANH-promoting operating mode. In an example, the normal operatingmode can be an ongoing normal ventricular pacing mode, such as VVI,VVIR, DDD, DDDR, DDI, DDIR, VDD, VDDR, VOO, or DOO. In another example,the normal operating mode can be an ongoing ventricular sensing modeduring which a subject's intrinsic ventricular beats are sensed and noventricular pacing is provided when an intrinsic ventricular beat issensed. In an example, the ANH-promoting operating mode can be a specialoperating mode that can include intermittent delivery of atrial stretchtherapy, which can include delivery of ventricular pacing pulses thatare synchronized to occur during an atrial diastole time period.

In an example, atrial diastole, which can be thought of as the timeperiod during which the atria are relaxed, can be detected, such as byusing an electrogram (EGM) or electrocardiogram (ECG). In an example, anintracardiac EGM can be detected using leads 108A-C and associatedelectrodes. The P-wave of an EGM or ECG can represent the wave ofdepolarization that spreads through the atria, causing them to contract.Thus, the P-to-P interval can be used to represent the total time of asingle cardiac cycle (e.g., the time from one heart beat to the next).Within the P-to-P interval, a specified time period, such as for example100 milliseconds, can be designated for atrial systole (e.g., the timeperiod when the atria are contracting). Once a specified time period hasbeen designated for atrial systole, the remainder of the P-to-P intervalcan be designated as atrial diastole. Thus, the atrial diastole timeperiod can be designated as the P-to-P interval time period minus theatrial systole time period.

In another example, the atrial diastole time period can be estimated asbeginning with first heart sound (“S1”) and extending for an intervaldefined by the S1-to-S1 interval minus a specified estimated or measuredatrial systolic interval (e.g., 100 ms). S1 is the vibrational soundmade by the heart when the AV valves (e.g., mitral and tricuspid valves)close. A second heart sound (“S2”) is the vibrational sound made by theheart when the semilunar valves (e.g., aortic and pulmonic valves)close. Although the time period between S1 and S2 can be used as ameasure of ventricular systole, it can also be used to estimate theatrial diastole time period.

When CRM device 100 is in the normal operating mode (e.g., under normalconditions), the ventricles can be paced or sensed during atrialsystole, such that the ventricles contract at the end of the atrialsystole time period, mimicking a normal physiologic cardiac cycle. In anexample, a normal cardiac cycle can be defined as the time periodbetween one ventricular contraction and the next ventricularcontraction. When CRM device 100 is in the ANH-promoting operating mode,the ventricles can generally be paced or sensed as in the normaloperating mode, but, intermittently, ventricular pacing pulses can bedelivered during an atrial diastole time period, such thatintermittently the ventricles contract at the beginning of atrialsystole or before atrial systole. This intermittent, specializedventricular pacing can be referred to as “ANH pacing” or “ANH pacingcycle(s).”

An example of a method of configuring CRM device 100 to synchronize thetiming of the ventricular pace on an atrial sensed or paced eventincludes utilization of a NASPE/BPEG (North American Society of Pacingand Electrophysiology/British Pacing and Electrophysiology Group) pacingmode. Pacing modes that do not synchronize the timing of the ventricularpace on a sensed or paced atrial event include, for example, VOO, VVIand VVIR. Pacing modes that can synchronize the timing of theventricular pace on an atrial sensed or paced event include, forexample, DDI, VDD, DDD, VDDR, DDDR.

There can be methods other than utilization of a NASPE/BPEG pacing modeby which the ventricular pace can be synchronized to an atrial event. Anatrial event can be determined via a measurement other than detection ofa p-wave or delivery of an atrial pace. For example, a blood pressure orthoracic impedance measurement can be used to determine an atrial event,such as described in Pederson et al. U.S. Pat. No. 5,137,019 entitled“VARIATION IN CARDIAC CHAMBER VOLUME OR PRESSURE AS A CONTROLLINGPARAMETER, assigned to the assignee of the present patent application,the disclosure of which is incorporated herein by reference in itsentirety. The timing of the ventricular pace can then be synchronized tothe blood pressure or thoracic impedance measurement.

FIGS. 3A-3C are schematic diagrams illustrating generally examples ofspecialized ventricular pacing that can be used to provide atrialstretch therapy. In the examples shown in FIGS. 3A-C, the CRM device 100is in the ANH-promoting operating mode. In FIG. 3A, a time period 302represents a first normal cardiac cycle and a time period 306 representsa second normal cardiac cycle. During time periods 302 and 306, the CRMdevice 100 can deliver ventricular pacing pulses at the end of atrialsystole. In an example, during time periods 302 and 306, the CRM device100 can sense, rather than pace, ventricular contraction events near theend of atrial systole. Similarly, although the atrial contraction eventsshown during the time periods 302 and 306 are sensed events, theseatrial events can be paced events in some examples. As shown at 304 and308, respectively, the AV delay in a normal cardiac cycle (e.g., thedelay between a sensed atrial event and a paced ventricular event) canbe a positive value, such as a value that is between about 10-400milliseconds, inclusive, for example.

The time period 310A represents an ANH pacing cycle. During the timeperiod 310A, the CRM device 100 can deliver ventricular pacing pulsesduring atrial diastole. As shown at 310A, during ANH pacing, ventricularsystole and atrial systole can substantially overlap. In the exampleshown at 310A, a ventricular pace is delivered before an atrial pace. Asshown at 312A, this creates a negative AV delay. Because a ventricularcontraction causes the AV valves to close, ANH pacing can result in theatria contracting against closed AV valves. As blood-filled atriacontract against closed AV valves, atrial pressure can increase, causingatrial stretch. Atrial stretch, in turn, can augment the production andrelease of ANH.

ANH release can be beneficial, and, in an example, ANH pacing can bedelivered continuously. However ANH pacing can be less efficient ifperformed for extended periods of time due to inefficient heart pumping,which can cause a decrease in cardiac output. Therefore, in an example,during the ANH-promoting mode of operation of CRM device 100, ANH pacingcan be delivered intermittently, such as by using ANH pacing for a timeperiod of about N minutes, and repeating every M minutes while in theANH-promoting operating mode where, for example, N can be 3 and M can be60. In another example, N can be less than one. In an example,intermittent ANH pacing can be accomplished by delivering X ANH pacingcycles for every Y total cycles where, for example, X can be 5 and Y canbe 100. In an example, the Y cycles can be contiguous; in anotherexample, the Y cycles can be non-contiguous.

In an example, intermittent ANH pacing can be accomplished by using bothtime periods and pacing cycles. For example, ANH pacing can be enabled 3minutes out of every 60 minutes, and during the 3 minutes that ANHpacing is enabled, ANH pacing can be delivered 5 out of every 100cycles. In yet another example, intermittent ANH pacing can beaccomplished by delivering a specified number of ANH pacing pulsesduring a 24-hour period.

As described above, the dose of ANH pacing therapy can be altered byadjusting the intermittency of ANH pacing. The dose of ANH pacingtherapy can also be altered by adjusting the amount of overlap betweenatrial and ventricular systoles. In an example, adjusting the overlapcan be accomplished by changing the timing of the ventricular pacing. Inanother example, adjusting the overlap can be accomplished by changingone or more ventricular pacing sites. In yet another example, the doseof ANH therapy can be altered by adjusting two or more of theintermittency of ANH pacing, the timing of the ventricular pacing, andthe location of ventricular pacing sites.

In FIG. 3B, time periods 302 and 306 represent normal cardiac cycles, asdescribed above with respect to FIG. 3A. The time period 310B representsan ANH pacing cycle during which a ventricular pacing pulse is deliveredat the very end of atrial diastole, such that the paced ventricularcontraction is substantially concurrent with a sensed or paced atrialcontraction. Thus, as shown at 312B, the AV delay can be approximatelyzero. Concurrent contraction of the atria and ventricles can result inblood-filled atria contracting against closed AV valves, which can causeatrial stretch and, consequently, increased secretion of ANH, such asdescribed above.

In FIG. 3C, time periods 302 and 306 represent normal cardiac cycles,such as described above with respect to FIG. 3A. The time period 310Crepresents an ANH pacing cycle during which a ventricular pacing pulseis delivered during atrial diastole and in anticipation of a sensedintrinsic atrial event. In this case, because a ventricular pace isdelivered before a sensed atrial beat, there is a negative AV delay,such as shown at 312C. As previously described, this can result inblood-filled atria contracting against closed AV valves, which can causeatrial stretch and, consequently, can cause increased secretion of ANH.

Although the examples in FIGS. 3A-C shows two normal cardiac cyclesoccurring before an ANH pacing cycle, there can be any number of normalcycles before an ANH pacing cycle occurs. Likewise, there can be one ormore consecutive or non-consecutive ANH pacing cycles. In an example,there can be one or more transition cycles between a normal cardiaccycle and an ANH pacing cycle, such as described below with respect toFIG. 4.

FIG. 4 is a schematic diagram illustrating additional details of the ANHpacing example shown in FIG. 3A above. In the example shown in FIG. 4,the CRM device 100 is in the ANH-promoting operating mode. The timeperiod 402 represents a normal cardiac cycle during normal ventricularpacing, such as described above with respect to FIGS. 3A-C. During thetime period 402, the CRM device 100 can deliver ventricular pacingpulses near the end of atrial systole. In an example, during the timeperiod 402, the CRM device 100 can sense, rather than pace, ventricularcontraction events at the end of atrial systole. Similarly, although theatrial event shown during time period 402 is a sensed atrial contractionevent, it can be a paced event in some examples. As shown at 404, AVdelay in a normal cardiac cycle (e.g., the delay between a sensed atrialevent and a paced ventricular event) can be a positive value, such asabout 10-400 milliseconds, for example. In an example, there can be oneor more normal cardiac cycles, such as that depicted by the time period402, before a transition to ANH pacing occurs.

The time period 406 represents a transition cycle from a normal cardiaccycle to an ANH pacing cycle. During the time period 406, the CRM device100 can deliver ventricular pacing pulses during atrial diastole. Thisresults in a negative AV delay 408, such as to provide atrial stretchand augmented ANH secretion, such as described above with respect toFIG. 3A. During the time period 406, ventricular diastole can beshortened with respect to a normal cardiac cycle. This can be a resultof the earlier occurrence of ventricular systole due to delivery of theventricular pacing pulse during atrial diastole (e.g., as opposed toduring atrial systole). Thus, during a transition from a normal cardiaccycle to ANH pacing, the ventricular interval can be shorter than theintrinsic atrial interval. In an example, there can be one or moretransition cycles, such as that depicted by the time period 406, beforeANH pacing begins. Although the atrial event shown during time period406 is a paced event, it can be a sensed event in some examples.

Time period 410 represents an example of an ANH pacing cycle. During thetime period 410, the CRM device 100 can deliver ventricular pacingpulses during atrial diastole. This results in a negative AV delay 412,such as to provide atrial stretch and augmented ANH secretion, such asdescribed above with respect to FIG. 3A. As shown during the time period410, ventricular diastole can lengthen with respect to ventriculardiastole during the transition cycle time period 406, and can return tothe length of ventricular diastole demonstrated during the normal cycletime period 402. This can be a result of ventricular “retiming,” inwhich the ventricular cycle can be reset such that ventricularcontraction events occur sooner with respect to corresponding atrialcontraction events. In an example, there can be one or more ANH pacingcycles, such as that depicted by the time period 410, before transitionback to a normal cardiac cycle occurs. Although the atrial event shownduring time period 410 is a paced event, it can be a sensed event insome examples.

The time period 414 can represent a transition cycle from an ANH pacingcycle to a normal cardiac cycle. During the time period 414, the CRMdevice 100 can deliver ventricular pacing pulses at the end of atrialsystole. In an example, during the time period 414, the CRM device 100can sense, rather than pace, ventricular events at the end of atrialsystole. Similarly, although the atrial contraction event shown duringthe time period 414 is a sensed event, it can be a paced event, in someexamples. As shown at 416, AV delay in a normal cardiac cycle can be apositive value, such as a value that is between about 10-400milliseconds, inclusive, for example. During the time period 414,ventricular diastole can be lengthened with respect to a normal cardiaccycle. This can be a result of the later occurrence of ventricularsystole, compared to during ANH pacing, due to delivery of theventricular pacing pulse during atrial systole (e.g., as opposed toduring atrial diastole). Thus, during the transition from ANH pacing toa normal cardiac cycle, the ventricular interval can be longer than theintrinsic atrial interval. In an example, there can be one or moretransition cycles, such as that depicted by the time period 414, beforea normal cardiac cycle resumes during the time period 402.

Without being bound by theory, it is believed that it may also bebeneficial to provide variability in the timing of the ANH cycle 410,such as to provide a ventricular pace concurrent with an atrial paceduring a particular ANH cycle 410 and then during the next ANH cycle 410to provide a ventricular pace just before the atrial pace and thenduring the next ANH cycle 410 to provide a ventricular pace just afterthe atrial pace, and so forth. Such variability can be deterministic,random, or pseudo-random in nature, such as can be determined by theprocessor circuit 212. Without being bound by theory, it is believedthat just variability or randomization can help inhibit or preventaccommodation or tolerance by the physiological mechanisms responsiblefor generating ANH. Such variability or randomization can be implementedwith respect to timing, as described above, or with respect torepetition rate, duty cycle, or any other parameter, such as forinhibiting or preventing such accommodation.

FIG. 5 illustrates generally an example including a method 500 fordelivering atrial stretch therapy such as via intermittent ANH pacing.In an example, the method 500 can be performed all or in part by usingthe CRM device 100 shown in FIG. 1. At 502, the CRM device 100 can beused to deliver ventricular pacing to a subject when in the normaloperating mode, such as described above with respect to FIGS. 3A-C.

At 504, a measure of one or more physiological parameters of the subjectcan be detected. Examples of a physiological parameter that can bedetected can include a measure of the subject's fluid status, such as apulmonary edema level, a peripheral edema level, or a blood pressure.Other examples of a physiological parameter that can be detected at 504can include one or more measures of the subject's hemodynamic status,such as heart rate, arrhythmia, cardiac output, canon wave, cardiaccontractility, pulmonary artery pressure, heart rate variability, orsympathetic nerve activity (e.g., renal nerve sympathetic activity).Further examples of one or more physiologic parameters that can bemeasured can include one or more blood gases, one or more electrolytes,creatinine, blood urea nitrogen (BUN), glucose, one or more natriureticpeptides, one or more heart sounds, or one or more respirations, or anycombination thereof. Another example of a physiologic parameter caninclude a measure a ventricular filling, such as by a thoracic impedancesensor. Another example of a physiologic parameter can include a measureof retrograde (e.g., ventricular to atrial) electrical conduction withinthe heart. In an example, the measure of a physiologic parameter caninclude a measure of the subject's physical activity level or posture,for example, using an accelerometer. In yet another example, the statusof a concomitant therapy, or the patient's response to the concomitanttherapy, can be measured in place of or in addition to the physiologicparameter. Examples of concomitant therapies include drug therapy,neural stimulation therapy, and cardiac resynchronization therapy.

At 506, it can be determined whether a first measured physiologicalparameter meets a criterion for triggering use of the ANH-promotingoperating mode, such as described above with respect to FIGS. 3A-C. Anexample of a criterion for triggering use of the ANH-promoting operatingmode can include a fluid overload condition (e.g., “hypervolemia”). Afluid overload condition can be determined, for example, by a level ofpulmonary edema or peripheral edema that that exceeds a specifiedthreshold value, such as by using an impedance-based or other fluidmonitoring technique. In an example, a fluid overload condition can bedetermined by a blood pressure (such as can be wirelessly communicatedfrom a separate pulmonary artery pressure (PAP) sensor) that exceeds aspecified threshold value.

In an example, a criterion for triggering use of the ANH-promotingoperating mode can include a fluid-underload condition (e.g.,“hypovolemia”), which can be detected similarly to the fluid overloadcondition, such as by using a thoracic impedance monitor, a PAP monitor,or other fluid monitoring technique. In an example, the ANH-promotingoperating mode can be used with the subject is euvolemic (e.g., neitherfluid-overloaded nor fluid-underloaded) because, without being bound bytheory, it is believed that there can be other benefits to using theANH-promoting operating mode. For example, ANH, when attached to NPR-Areceptors can obtain a variety of responses, such as vasodilation,enhanced lusitropy, anti-fibrosis, etc. Thus, the criterion fortriggering use of the ANH-promoting operating mode can include detectinga condition that could benefit from such a response to the ANH-promotingoperating mode. For example, detecting vasoconstriction of or beyond aspecified amount can trigger the ANH-promoting mode to triggerresponsive vasodilation. In an example, detecting or expecting increasedcardiac contractility (such as when cardiac contractility modulation(CCM) therapy is turned on) can trigger the ANH-promoting mode totrigger responsive lusitropy to promote adequate cardiac relaxation. Inan example, detecting or expecting increased myocardial fibrosis (e.g.,such as can be detected by monitoring an intracardiac or thoracicimpedance or otherwise) can trigger the ANH-promoting mode to trigger aresponsive anti-fibrotic property of ANH.

Examples of other criteria for triggering use of the ANH-promotingoperating mode can include one or more physiological parametermeasurements indicative of renal dysfunction due to heart failure, suchas elevated (e.g., above a normal physiologic range) creatinine or BUN,for example. In addition, use of the ANH-promoting operating mode can betriggered by a measure of one or more natriuretic peptides that is belowa specified threshold value.

At 506, if it is determined that a first measured physiologicalparameter meets a criterion for triggering use of the ANH-promotingoperating mode, then, at 508, it can be determined whether a secondmeasured physiological parameter meets a criterion for limiting (e.g.,inhibiting or avoiding) use of the ANH-promoting operating mode. In anexample, the first measured physiological parameter can be differentthan the second measured physiological parameter. In an example, thefirst and second physiological parameters can be the same physiologicalparameter. An example of a criterion for limiting use of theANH-promoting operating mode can include a measured indication ofcardiac output that is below a specified threshold value. Other examplesof criteria for limiting use of the ANH-promoting operating mode caninclude an indication of hypotension (e.g., blood pressure below aspecified threshold value), an elevated physical activity level, anelevated respiration level, a detected arrhythmia, bradycardic pacing,or the delivery of cardiac shock therapy within a specified period oftime (e.g. within the past day or within the past week). Under theseconditions, ANH pacing can be limited due to the temporary decrease incardiac output that can result from such temporary ANH pacing.

If, at 508, it is determined that a second measured physiologicalparameter does not meet a criterion for limiting use of theANH-promoting operating mode, then, at 510, use of the ANH-promotingoperating mode can be triggered. As described above with respect toFIGS. 3A-C, use of the ANH-promoting operating mode can includeintermittent delivery of ventricular pacing pulses during an atrialdiastole time period. Information about use of the ANH-promotingoperating mode can be stored in a memory of the CRM device orcommunicated to a user or automated process, such as to provide adiagnostic indication or for use in adjusting or otherwise controlling atherapy provided by the CRM device 100, or by another implanted,ambulatory, or other medical device, or by a physician or othercaregiver. Such communication can be internal to the electronics unit102 of the CRM device 100, or can involve communication with the localinterface 121 or with the remote interface 124. The acts described inFIG. 5 can be performed by the processor 212 or other circuitry in theelectronics unit 102 of the CRM device 100, or by a processor or othercircuitry associated with the local interface 121 or the remoteinterface 124, or using some combination of the CRM device 100, thelocal interface 121, or the remote interface 124.

At 510, use of the ANH-promoting mode can obtain the benefits describedherein that are associated with increased ANH release. The presentinventors have also recognized however, that delivering a ventricularpace during atrial diastole to promote ANH can lead to sub-optimalhemodynamics (e.g., reduced cardiac output) during the ANH-promotingmode. For example, if there is a risk that a subject with compromisedcardiac function may become hypotensive if atrial systolic function isimpacted by using the ANH promoting mode, one or more techniques toenhance cardiac output can optionally be incorporated into or used inconjunction with the ANH-promoting mode at 510.

For example, a cardiac-output compensated ANH-promoting mode at 510 caninclude triggering providing pacing at an increased heart rate before,during, or after the ANH-promoting mode at 510. This can help increasethe cardiac output during or temporally near the ANH-promoting mode at510, such as to compensate for what may otherwise be decreased cardiacoutput during the ANH-promoting mode. This can help inhibit or prevent asubject with compromised cardiac function from becoming hypotensiveduring the ANH-promoting mode at 510.

In an example, a cardiac-output compensated ANH-promoting mode at 510can include triggering cardiac contractility modulation (CCM) therapybefore, during, or after the ANH-promoting mode at 510. Examples of CCMare described in Stahmann U.S. patent application Ser. No. 12/561,124,entitled CARDIAC FUNCTION MANAGEMENT INTEGRATING CARDIAC CONTRACTILITYMODULATION, which was filed on Sep. 16, 2009, and which is incorporatedby reference herein in its entirety, including its description oftechniques (e.g., systems, methods, apparatus) of using CCM. Use of CCMcan help increase the cardiac output during or temporally near theANH-promoting mode at 510, such as to compensate for what may otherwisebe decreased cardiac output during the ANH-promoting mode. This can helpinhibit or prevent a subject with compromised cardiac function frombecoming hypotensive during the ANH-promoting mode at 510.

In an example, a cardiac-output compensated ANH promoting mode at 510can include initiating or changing a pharmacologic prescription (e.g.,dobutamine or adenosine) before using the ANH promoting mode at 510,such as to help temporarily increase cardiac output during theANH-promoting mode at 510, such as to inhibit or prevent the subjectfrom becoming hypotensive.

These are just examples of techniques that can be used to compensatecardiac output during or temporally near the ANH promoting mode, andother techniques can also be used, and such techniques need not belimited to only those subjects with compromised cardiac function, butcan be used in other patients.

At 504 and 506, the above description has emphasized detecting aphysiological parameter and comparing it to a criterion, such as todetermine whether one or more conditions exist for which ANH-promotingmay be useful. However, such detecting and determining can additionallyor alternatively be used to screen for or otherwise determine whetherappropriate conditions exist for delivering the ANH. This can be useful,for example, such as to mitigate or avoid one or more effects orside-effects of producing ANH when operating in the ANH promoting modeat 510.

For example, ANH can have a diuretic effect, with an accompanying urgeto urinate. Therefore, the engaging of the ANH promoting mode at 510 canbe timed so as not to cause inconvenience to the patient—which mightotherwise be the case if the ANH-promoting mode at 510 were scheduled tooccur before sleep or during early hours of sleep. In an example, asleep or posture detector can be used at 504 to determine or inferwhether a patient is sleeping. One example of a sleep detector isdescribed in Carlson et al., U.S. patent application Ser. No.09/802,316, entitled “CARDIAC RHYTHM MANAGEMENT SYSTEM USING TIME-DOMAINHEART RATE VARIABILITY INDICIA,” which is assigned to CardiacPacemakers, Inc., and which is incorporated herein by reference in itsentirety, including its description of a sleep detector. Another exampleof a sleep detector is described in Hatlestad et al., U.S. PatentApplication Serial No. 2004/0073128, entitled “DETECTION OF CONGESTIONFROM MONITORING PATIENT RESPONSE TO RECUMBENT POSITION,” which isassigned to Cardiac Pacemakers, Inc., and which is incorporated hereinby reference in its entirety. In an example, the sleep detector can beused to detect a specified sleep stage measure, such as non-rapid eyemovement sleep, such as described in Stahmann et al. U.S. Pat. No.7,572,225 entitled “SLEEP LOGBOOK,” and Quan et al. U.S. Pat. No.7,189,204 entitled “SLEEP DETECTION USING AN ADJUSTABLE THRESHOLD,” bothassigned to the assignee of the present patent application, thedisclosures of which are incorporated herein by reference in theirentirety. Sleep can also be inferred from information about physicalactivity, which can be detected, for example, using an accelerometer804. Sleep can also be inferred from information about posture and angleof reclination, which can be detected using a posture detector 806, suchas described in Wang et al. U.S. patent application Ser. No. 11/283,490entitled “POSTURE DETECTOR CALIBRATION AND USE,” which published on May24, 2007 as Publication No. 2007/0118056, assigned to the assignee ofthe present patent application, the disclosure of which is incorporatedherein by reference in its entirety.

Sleep status information can be used to schedule the ANH promoting modeat 510 to occur when the patient is awake, such as when the patient hasjust woken up, or just before the patient is expected to awake.Time-of-day information can constitute physiological information in thesense that it can indicate where a subject is in terms of a physiologicdaily circadian rhythm. Such time-of-day information can additionally oralternatively be used, such as to time the scheduling of the ANHpromoting mode at 510 to occur at an appropriate time of day, such as toappropriately coincide with the subject's circadian rhythm. Similarly,one or more other physiological conditions can be sensed at 504 andcompared at 506, such as to determine whether a condition exists thatindicates or contraindicates use of the ANH promoting mode at 510, sothat such ANH promoting mode at 510 can be inhibited or triggered, asdeemed appropriate based upon such information.

The techniques (e.g., systems, methods, apparatus) described herein canbe used in conjunction with one or more other techniques for treatingcongestive heart failure, such as in a combination CRM device 100. Suchother techniques can include, for example, one or any combination of:cardiac resynchronization therapy (CRT), such as for providingbiventricular or intraventricular or other spatial coordination of aheart contraction, His bundle pacing for providing right ventricular CRTwithout requiring a coronary sinus or other left ventricular lead,diuretic or other drug therapy, or neurostimulation therapy such asvagal stimulation. An example of techniques for providing vagal or otherneurostimulation, such as for treating congestive heart failure, isdescribed in Moffitt et al. U.S. Pat. No. 7,499,748 entitledTRANSVASCULAR NEURAL STIMULATION DEVICE, the application for which wasfiled on Apr. 11, 2005, and which issued on Mar. 3, 2009, which isincorporated by reference herein in its entirety, including itsdescription of techniques for providing neurostimulation, which can beused in a combination device with the present subject matter. Anotherexample of techniques for providing vagal or other neurostimulation,such as for treating congestive heart failure, is described in Libbus etal. U.S. patent application Ser. No. 11/382,128, which was filed on May8, 2006, and which published on Nov. 8, 2007 as Publication No.2007/0260285, each of which is incorporated by reference herein in itsentirety, including its description of techniques for providingneurostimulation, which can be used in a combination device with thepresent subject matter.

Additional Notes

The above detailed description includes references to the accompanyingdrawings, which form a part of the detailed description. The drawingsshow, by way of illustration, specific embodiments in which theinvention can be practiced. These embodiments are also referred toherein as “examples.” Such examples can include elements in addition tothose shown or described. However, the present inventors alsocontemplate examples in which only those elements shown or described areprovided. Moreover, the present inventors also contemplate examplesusing any combination or permutation of those elements shown ordescribed (or one or more aspects thereof), either with respect to aparticular example (or one or more aspects thereof), or with respect toother examples (or one or more aspects thereof) shown or describedherein.

All publications, patents, and patent documents referred to in thisdocument are incorporated by reference herein in their entirety, asthough individually incorporated by reference. In the event ofinconsistent usages between this document and those documents soincorporated by reference, the usage in the incorporated reference(s)should be considered supplementary to that of this document; forirreconcilable inconsistencies, the usage in this document controls.

In this document, the terms “a” or “an” are used, as is common in patentdocuments, to include one or more than one, independent of any otherinstances or usages of “at least one” or “one or more.” In thisdocument, the term “or” is used to refer to a nonexclusive or, such that“A or B” includes “A but not B,” “B but not A,” and “A and B,” unlessotherwise indicated. In the appended claims, the terms “including” and“in which” are used as the plain-English equivalents of the respectiveterms “comprising” and “wherein.” Also, in the following claims, theterms “including” and “comprising” are open-ended, that is, a system,device, article, or process that includes elements in addition to thoselisted after such a term in a claim are still deemed to fall within thescope of that claim. Moreover, in the following claims, the terms“first,” “second,” and “third,” etc. are used merely as labels, and arenot intended to impose numerical requirements on their objects.

The above description is intended to be illustrative, and notrestrictive. For example, the above-described examples (or one or moreaspects thereof) may be used in combination with each other. Otherembodiments can be used, such as by one of ordinary skill in the artupon reviewing the above description. The Abstract is provided to complywith 37 C.F.R. §1.72(b), to allow the reader to quickly ascertain thenature of the technical disclosure. It is submitted with theunderstanding that it will not be used to interpret or limit the scopeor meaning of the claims. Also, in the above Detailed Description,various features may be grouped together to streamline the disclosure.This should not be interpreted as intending that an unclaimed disclosedfeature is essential to any claim. Rather, inventive subject matter maylie in less than all features of a particular disclosed embodiment.Thus, the following claims are hereby incorporated into the DetailedDescription, with each claim standing on its own as a separateembodiment. The scope of the invention should be determined withreference to the appended claims, along with the full scope ofequivalents to which such claims are entitled.

The claimed invention is:
 1. An apparatus comprising: a cardiac rhythmmanagement device comprising: a ventricular pacing circuit, configuredto deliver a ventricular pace; an atrial pacing circuit, configured todeliver an atrial pace; and a processor circuit, coupled to theventricular circuit and the atrial pacing circuit, the processorconfigured to comprise a first operating mode, the processor configuredto time delivery of the ventricular pace, when in the first operatingmode, so that: (1) delivery of the ventricular pace is synchronized tooccur during an atrial diastole time period, and (2) delivery of theventricular pace results in a substantial overlap of ventricular systoleand atrial systole; so that a paced ventricular contraction occursbefore a paced atrial contraction during the same cardiac cycle.
 2. Theapparatus of claim 1, wherein the processor is configured to timedelivery of the ventricular pace, when in the first operating mode, tocause atrioventricular valve closure during at least one of: earlyatrial systole or a specified period of time before atrial systole. 3.The apparatus of claim 1, comprising: an atrial sensing circuit, coupledto the processor, and configured to sense an atrial heart signal, andwherein the atrial sensing circuit is coupled to the processor; andwherein the processor is configured to time delivery of the ventricularpace, when in the first mode of operation, such that a paced ventricularcontraction occurs before a sensed atrial contraction during the samecardiac cycle.
 4. The apparatus of claim 1, wherein the processor isconfigured to time delivery of the ventricular pace, when in the firstmode of operation, so that a paced ventricular contraction issubstantially concurrent with a paced or sensed atrial contractionduring the same cardiac cycle.
 5. The apparatus of claim 1, comprising:a physiologic sensor, coupled to the processor, the physiologic sensorconfigured to measure a physiologic parameter of a subject; wherein theprocessor is configured to adjust use of the first operating mode usinginformation about the measure of the physiologic parameter.
 6. Theapparatus of claim 1, comprising: a physical activity sensor, coupled tothe processor, the physical activity sensor configured to detectphysical activity of a subject; wherein the processor is configured tolimit use of the first mode of operation to when the physical activityis above a specified threshold value.
 7. The apparatus of claim 1,comprising: a cardiac output monitor circuit, coupled to the processor,the cardiac output monitor circuit configured to provide an indicationof a cardiac output of the subject; and wherein the processor isconfigured to limit use of the first mode of operation to when theindication of the cardiac output is below a specified threshold value.8. The apparatus of claim 1, comprising: a fluid status monitor circuit,coupled to the processor, the fluid status monitor circuit configured tomonitor a fluid status providing an indication of a fluid status of thesubject; and wherein the processor is configured to use informationabout the fluid status of the subject to trigger use of the firstoperating mode.
 9. The apparatus of claim 8, wherein the processor isconfigured to adjust use of the first operating mode when the fluidstatus indicates at least one of: (1) a fluid overload condition, or (2)a fluid underload condition.
 10. The apparatus of claim 8, wherein thefluid status monitor circuit is configured to monitor the fluid statususing a pulmonary artery pressure (PAP) signal received from a PAPsensor.
 11. The apparatus of claim 1, wherein the processor circuit isconfigured to alter a delivery time of the ventricular pace, when in thefirst operating mode, to provide variability, with respect to an atrialcontraction time, over a plurality of the ventricular paces.
 12. Theapparatus of claim 1, wherein the processor is configured to alter aventricular pacing site.
 13. The apparatus of claim 1, wherein theprocessor is configured to adjust delivery of a therapy to offset adecrease in cardiac output otherwise associated with the first operatingmode.
 14. The apparatus of claim 1, wherein the processor is configuredto at least one of trigger or inhibit the first operating mode at leastin part using information about a detected physiological condition. 15.The apparatus of claim 14, wherein the processor is configured to atleast one of trigger or inhibit the first operating mode at least inpart using information about a time of day.
 16. The apparatus of claim14, wherein the processor is configured to at least one of trigger orinhibit the first operating mode at least in part using informationabout a posture.
 17. The apparatus of claim 14, wherein the processor isconfigured to at least one of trigger or inhibit the first operatingmode at least in part using information about a sleep state.
 18. Anapparatus comprising: a cardiac rhythm management device comprising: aventricular pacing circuit, configured to deliver a ventricular pace; aprocessor circuit, coupled to the ventricular pacing circuit, theprocessor configured to comprise a first operating mode, the processorconfigured to time delivery of the ventricular pace, when in the firstoperating mode, so that: (1) delivery of the ventricular pace issynchronized to occur during an atrial diastole time period, (2)delivery of the ventricular pace results in a substantial overlap ofventricular systole and atrial systole, and (3) atrioventricular valveclosure is caused during at least one of: early atrial systole or aspecified period of time before atrial systole; a physiologic sensor,coupled to the processor, the physiologic sensor configured to measureat least three physiologic parameters of a subject including a physicalactivity, a cardiac output, and a fluid status; wherein the processor isconfigured to adjust use of the first operating mode using informationabout the measure of the physiologic parameter, including usinginformation about the fluid status and including limiting use of thefirst mode of operation to when the physical activity is above aspecified threshold value and to when cardiac output is below aspecified threshold value; and wherein the processor is configured toprovide variability in the first operating mode to inhibit or preventaccommodation of the subject to the first operating mode.
 19. Theapparatus of claim 18, wherein the processor is configured to adjustdelivery of a therapy to offset a decrease in cardiac output otherwiseassociated with the first operating mode.
 20. The apparatus of claim 18,wherein the processor is configured to at least one of trigger orinhibit the first operating mode at least in part using time of day,posture, or sleep status information.
 21. An apparatus comprising: acardiac rhythm management device comprising: a ventricular pacingcircuit, configured to deliver a ventricular pace; a processor circuit,coupled to the ventricular pacing circuit, the processor configured tocomprise a first operating mode, the processor configured to timedelivery of the ventricular pace, when in the first operating mode, suchthat: (1) delivery of the ventricular pace is synchronized to occurduring an atrial diastole time period, and (2) delivery of theventricular pace results in a substantial overlap of ventricular systoleand atrial systole; an atrial pacing circuit configured to deliver anatrial pace, and wherein the atrial pacing circuit is coupled to theprocessor; and wherein the processor is configured to time delivery ofthe ventricular pace, when in the first operating mode, so that a pacedventricular contraction occurs before or substantially concurrent with apaced atrial contraction during the same cardiac cycle.